This Phase I proposal aims to develop a unique class of nanostructured smart lidocaine gels for site-specific pain management. The hypothesis for the design and testing of this gel system is based on two recent findings. (1) Medicated smart gels, containing lidocaine (an anesthetic drug) and mixtures of pluronic-based block copolymers (poly (ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)) in water, can be fine-tuned by copolymer composition and concentration to possess thermo reversible gelation behavior near the body temperature. Such characteristics will enable the sustained and controlled release of lidocaine molecules and can facilitate site deployment pathways (e.g. low pressure spraying, injection or topical coating). (2) The dynamic formation of microscopic bioabsorbable medicated particles (micron and submicron sizes) based on polyelectrolyte complex formation (e.g., mixtures based on chitosan and alginate) can provide a sustained release of lidocaine to tens of days. To test the above hypothesis, three specific aims have been proposed to verify the scientific merits and technical feasibility of the approach. Specific Aim 1: Characterize and optimize therapeutic mixtures of lidocaine-pluronic smart gels and lidocaine containing polyelectrolyte complex particles with sustained lidocaine release capability (from days to weeks or perhaps even months). Specific Aim 2: In vitro assessments of the therapeutic efficacies of mixtures of lidocaine-pluronic smart gels, lidocaine-containing polyelectrolyte complex particles, and smart gels containing such complex particles. Specific Aim 3: Determination of the relative in vivo efficacies of lidocaine-containing smart gels by using two rat models based on the hot-plate test and the tail-flick test. The strength of the proposed system is its ability to manage pain through controlled and sustained release of local anesthetics at the injury site. The persistence of chronic pain can affect many different aspects of personal life, ranging from the physiological to societal and financial changes. This proposal aims to develop a unique class of smart lidocaine gels for pain management. The strength of the proposed system is its ability to manage pain through controlled and sustained release of local anesthetics at the injury site. [unreadable] [unreadable] [unreadable]